For decades the public health community has tried to devise a vaccine that would confer lifetime immunity against the malaria parasite and help stamp out disease. Yet the effort has always been an exercise in frustration. The complex life cycle of the parasite makes it challenging to know the best way to create an effective vaccine. But the advent of new funding and a spate of innovative ideas have changed the out­look dramatically in recent years. For the first time, a vaccine has reached late-stage clinical trials, and dozens of other ideas are in the early development stage. Three different approaches appear here.

1. Blocking Transmission

The vaccine, given to a person, would elicit production of antibodies that would pass into the gut of a feasting mosquito, where they would prevent the parasite from interacting with an enzyme needed for survival. Next time the mosquito bit someone, it would have no malaria parasites to transmit.

2. Culturing Weak Parasites

To create new vaccines, researchers often take an infectious agent, weaken it in some way and then inject pieces of the organism into humans to produce an immune reaction. One company—Seattle BioMed—uses exactly this approach, irradiating parasites in the sporozoite stage, to prevent them from maturing, and then injecting parasite fragments into patients. In early human trials, this vaccine has achieved 100 percent immune protection against malaria.

3. Boosting a Traditional Vaccine

A vaccine from GlaxoSmithKline has entered late-stage clinical trials against Plasmodium falciparum, a deadly species of the parasite. An earlier version of the vaccine failed in clinical trials, but it was reformulated with a chemical, an adjuvant, that enhances the immune response. The newer version appears to reduce an individual’s chance of getting the severe form of the disease by about half, an unprecedented statistic for a malaria vaccine this close to commercial availability.